It is the objective of the proposed research to assign gene loci to chromosome regions by gene-chromosome linkage analysis in interspecific somatic cell hybrids. By hybridizing cells from individuals carrying chromosome translocations or deletions, we plan to map gene loci which are known to be on the rearranged chromosomes to chromosomal subregions. The 33 different reciprocal translocations and deletions available for cell fusion experiments have been studied with banding techniques; the points of chromosome breakage and rejoining have been established. Hybridization experiments with several rearrangements involving the same chromosome but with different breakpoints will provide insight into the distribution and linear order of genes on chromosomes. A second approach to intrachromosomal gene mapping makes use of the expected correlation between the number of gene copies present in a cell and the amount of detectable gene product (gene-dose effect). By measuring levels of enzyme activity in red blood cells from individuals with duplications or deletions of defined chromosomal regions, gene loci can be assigned to the affected chromosome regions. By hybridization of cells expressing differentiated functions (e.g., from a hepatoma or adrenal carcinoma), gene loci involved in control of expression of these functions can be mapped. Activation of the human genes for differentiated functions in interspecific hybrids between differentiated non-human and undifferentiated human cells can lead to chromosomal assignments of the human genes for "specialized" functions.